To explore the underlying mechanism of Xiaoyao Powder in the treatment of premenstrual syndrome based on network pharmacology.Methods:The core components and targets of Xiaoyao Powder were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine(BATMAN-TCM).The targets of the premenstrual syndrome were predicted by relevant databases.Venn diagram was used to obtain the common targets of Xiaoyao Powder and the disease.Cytoscape was used to construct the “component-target-disease” network.STRING was used for the analysis of protein-protein interaction(PPI).The common targets of Xiaoyao Powder and the disease were analyzed by Gene Ontology(GO) enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment on DAVID.Results:A total of 162 active components and 2 618 predicted targets of Xiaoyao Powder and 768 targets related to premenstrual syndrome were obtained.Twenty-one common targets were obtained through Venn diagram.Forty-three biological processes were screened out，involving signal transduction，transcription initiation of RNA polymerase Ⅱ，negative regulation of I-κB kinase/NF-κB signaling，and negative regulation of apoptosis.Meanwhile，17 signaling pathways were screened out，including the HIF-1 signaling pathway.Conclusion:Xiaoyao Powder may treat premenstrual syndrome by regulation of hormones，hypothalamic-pituitary-adrenal axis，and neurotransmitters，and anti-depression.